Treatment of Prader-Willi Syndrome
Prader-Willi syndrome (PWS) requires a multidisciplinary approach with sleep management, growth hormone therapy, strict dietary controls, and behavioral interventions as the cornerstones of treatment to reduce morbidity and mortality and improve quality of life. 1
Core Treatment Components
Growth Hormone Therapy
- First-line treatment for children with PWS
- Benefits: Improves lean body mass, motor development, body composition, and linear growth 1, 2
- Can begin as early as 2-3 months of age (though FDA approved for children >2 years with documented growth failure) 1
- Required monitoring:
- Polysomnography before starting and 6-10 weeks after initiation
- IGF-1 levels at least twice yearly
- Head circumference at each visit 1
- Contraindications: Severe obesity, history of upper airway obstruction, sleep apnea, or severe respiratory impairment 3
Sleep Disorder Management
- All patients should be evaluated annually for:
- Sleep-disordered breathing
- Excessive daytime sleepiness
- Narcolepsy and cataplexy
- Insomnia 1
- Indications for sleep evaluation:
- Rapid weight gain
- Change in school performance
- New attention concerns
- Worsening daytime sleepiness
- Increased irritability
- Developmental stagnation 1
- Testing approach:
- Polysomnography for sleep-disordered breathing
- Sleep diary, actigraphy, and Multiple Sleep Latency Test for excessive daytime sleepiness 1
Nutritional and Weight Management
- Phase-specific approach:
- Environmental controls:
- Lock cabinets and refrigerators
- Limit food exposures
- Maintain consistent meal routines 1
- Medication considerations:
- Limited evidence for anti-obesity medications (metformin, topiramate, liraglutide, setmelanotide)
- No widely accepted consensus guidelines for these medications in children with PWS 2
Endocrine Management
- Evaluate and treat:
- For undescended testes: Trial of human chorionic gonadotropin (hCG) before surgery 1
- Consider early morning serum adrenocorticotropic hormone and cortisol evaluations 1
Behavioral Management
- Address age-specific behavioral challenges:
- Early childhood: Rigidity and temper tantrums
- Later childhood: Perseverant speech and compulsive behaviors
- Adolescence: Food-seeking behaviors, lying, and stealing 1
- For compulsivity and maladaptive behaviors:
- Structured, predictable routines
- Behavioral programming
- Support during transitions
- Family support
- Consider SSRIs for skin picking, compulsivity, and aggressive episodes
- Consider atypical antipsychotics for extreme aggression or psychosis 5
Multidisciplinary Care Team
A comprehensive care team should include:
- Pediatric endocrinologist
- Sleep specialist
- Nutritionist/dietician
- Psychologist
- Neurologist/neuropsychiatrist
- ENT specialist
- Pulmonologist
- Dentist
- Orthopedist
- Ophthalmologist 6
Common Pitfalls and Caveats
- Growth hormone risks: Monitor closely for sleep apnea after initiation; deaths have occurred in children with PWS within 6 months of starting therapy 1
- Glucose intolerance: GH therapy may decrease insulin sensitivity; monitor glucose levels regularly 3
- Respiratory vulnerability: Abnormal ventilatory responses to hypercapnia and hypoxia increase risk; maintain low threshold for respiratory evaluation 1
- Psychiatric disorders: Increased risk for obsessive-compulsive disorder, tantrums, aggression, and psychotic disorders (especially in young adults) 5
- Feeding in infancy: Avoid gastrostomy tubes when possible as poor feeding is transient in PWS 1
Early diagnosis, prompt initiation of appropriate therapies, and comprehensive multidisciplinary care are essential to improve outcomes and quality of life for individuals with PWS.